OA12293A - 3-Azabicyclo(3.1.0)hexane derivatives having opioid receptor affinity. - Google Patents

3-Azabicyclo(3.1.0)hexane derivatives having opioid receptor affinity. Download PDF

Info

Publication number: OA12293A
Authority: OA; OAPI
Prior art keywords: alkyl; aryl; halogen; optionally substituted; substituted
Prior art date: 2000-06-23

Application number

OA1200200386A

Other languages

English (en)

Inventor

Bernard Joseph Banks

Douglas James Critcher

Ashley Edward Fenwick

David Morris Gethin

Stephen Paul Gibson

Graham Lunn

Original Assignee

Pfizer

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.)

2000-06-23

Filing date

2001-06-07

Publication date

2004-03-18

2001-06-07 Application filed by Pfizer filed Critical Pfizer

2004-03-18 Publication of OA12293A publication Critical patent/OA12293A/en

Links

108090000137 Opioid Receptors Proteins 0.000 title abstract description 11
102000003840 Opioid Receptors Human genes 0.000 title abstract description 11
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238000011282 treatment Methods 0.000 claims abstract description 19
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238000000034 method Methods 0.000 claims description 101
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238000006243 chemical reaction Methods 0.000 claims description 51
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VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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230000007246 mechanism Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
FXWHFKOXMBTCMP-WMEDONTMSA-N milbemycin Natural products COC1C2OCC3=C/C=C/C(C)CC(=CCC4CC(CC5(O4)OC(C)C(C)C(OC(=O)C(C)CC(C)C)C5O)OC(=O)C(C=C1C)C23O)C FXWHFKOXMBTCMP-WMEDONTMSA-N 0.000 description 1
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238000002156 mixing Methods 0.000 description 1
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NUDGACANKYSDOG-UHFFFAOYSA-N n-[3-(6-ethyl-3-azabicyclo[3.1.0]hexan-6-yl)phenyl]methanesulfonamide Chemical compound C12CNCC2C1(CC)C1=CC=CC(NS(C)(=O)=O)=C1 NUDGACANKYSDOG-UHFFFAOYSA-N 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
239000008188 pellet Substances 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
229920001343 polytetrafluoroethylene Polymers 0.000 description 1
239000004810 polytetrafluoroethylene Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
235000011118 potassium hydroxide Nutrition 0.000 description 1
229940093932 potassium hydroxide Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000004540 pour-on Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
229960005205 prednisolone Drugs 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
SYBXSZMNKDOUCA-UHFFFAOYSA-J rhodium(2+);tetraacetate Chemical compound [Rh+2].[Rh+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O SYBXSZMNKDOUCA-UHFFFAOYSA-J 0.000 description 1
239000000523 sample Substances 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
239000002453 shampoo Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
241000894007 species Species 0.000 description 1
239000004544 spot-on Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000000725 suspension Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
238000012360 testing method Methods 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000011426 transformation method Methods 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
238000005406 washing Methods 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
239000011592 zinc chloride Substances 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
- 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
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Neurosurgery (AREA)
Addiction (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Dermatology (AREA)
Hospice & Palliative Care (AREA)
Otolaryngology (AREA)
Gynecology & Obstetrics (AREA)
Nutrition Science (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

OA1200200386A 2000-06-23 2001-06-07 3-Azabicyclo(3.1.0)hexane derivatives having opioid receptor affinity. OA12293A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GBGB0015562.2A GB0015562D0 (en)	2000-06-23	2000-06-23	Heterocycles

Publications (1)

Publication Number	Publication Date
OA12293A true OA12293A (en)	2004-03-18

Family

ID=9894368

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200200386A OA12293A (en)	2000-06-23	2001-06-07	3-Azabicyclo(3.1.0)hexane derivatives having opioid receptor affinity.

Country Status (34)

Country	Link
EP (1)	EP1292574A1 (is)
JP (1)	JP2004512263A (is)
KR (1)	KR20040002386A (is)
CN (1)	CN1639121A (is)
AP (1)	AP2002002698A0 (is)
AR (1)	AR028969A1 (is)
AU (1)	AU781837B2 (is)
BG (1)	BG107329A (is)
BR (1)	BR0111867A (is)
CA (1)	CA2412188A1 (is)
CZ (1)	CZ20023967A3 (is)
DO (1)	DOP2001000187A (is)
DZ (1)	DZ3368A1 (is)
EA (1)	EA005117B1 (is)
GB (1)	GB0015562D0 (is)
HR (1)	HRP20020998A2 (is)
HU (1)	HUP0301228A3 (is)
IL (1)	IL153427A0 (is)
IS (1)	IS6637A (is)
MA (1)	MA26915A1 (is)
MX (1)	MXPA02012878A (is)
NO (1)	NO20026168L (is)
NZ (1)	NZ523141A (is)
OA (1)	OA12293A (is)
PA (1)	PA8519401A1 (is)
PE (1)	PE20020253A1 (is)
PL (1)	PL365956A1 (is)
SK (1)	SK17172002A3 (is)
TN (1)	TNSN01094A1 (is)
UA (1)	UA73176C2 (is)
UY (1)	UY26787A1 (is)
WO (1)	WO2001098267A1 (is)
YU (1)	YU91802A (is)
ZA (1)	ZA200210278B (is)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PL368919A1 (en) *	2001-10-22	2005-04-04	Pfizer Products Inc.	3-azabicyclo (3.1.0) hexane derivatives as opioid receptor antagonists
CN101310723A (zh) *	2002-05-17	2008-11-26	迪欧加药品公司	有效的选择性阿片受体调制剂化合物的用途
DE10259245A1 (de)	2002-12-17	2004-07-01	Merck Patent Gmbh	Derivate des Asimadolins mit kovalent gebundenen Säuren
TW200538113A (en) *	2004-02-23	2005-12-01	Glaxo Group Ltd	Compounds
GB0507680D0 (en) *	2005-04-15	2005-05-25	Glaxo Group Ltd	Compounds
WO2006133945A1 (en) *	2005-06-14	2006-12-21	Glaxo Group Limited	Novel compounds
DE602007012531D1 (de) *	2006-04-03	2011-03-31	Glaxo Group Ltd	Azabicycloä3.1.0ühexanderivate als modulatoren von dopamin-d3-rezeptoren
AU2008232954A1 (en)	2007-03-30	2008-10-09	Tioga Pharmaceuticals Inc.	Kappa-opiate agonists for the treatment of diarrhea-predominant and alternating irritable bowel syndrome
TWI423801B (zh) *	2007-08-27	2014-01-21	Theravance Inc	作為μ類鴉片受體拮抗劑之８－氮雜雙環〔３．２．１〕辛基－２－羥基苯甲醯胺化合物
EP2580201B1 (en)	2010-06-11	2017-08-02	Rhodes Technologies	Transition metal-catalyzed processes for the preparation of n-allyl compounds and use thereof
EP2621902B1 (en)	2010-09-28	2017-04-12	Panacea Biotec Ltd	3-azabicyclo[3.1.0]hexane compounds useful for the treatment of cns disorders
KR102305244B1 (ko) *	2013-11-20	2021-09-27	우베 고산 가부시키가이샤	신규 3-아자비사이클로[3.1.0]헥산 유도체 및 그 의약 용도
KR20180004734A (ko)	2015-05-20	2018-01-12	가부시키가이샤산와카가쿠켄큐쇼	신규 3-아자비시클로［3.1.0］헥산 유도체의 염의 결정 및 그의 의약 용도
KR102662065B1 (ko)	2017-02-17	2024-05-07	트레베나, 인코포레이티드.	7-원 아자-헤테로고리 함유 델타-오피오이드 수용체 조절 화합물, 및 그의 사용 및 제조 방법
WO2018152293A1 (en)	2017-02-17	2018-08-23	Trevena, Inc.	5-membered aza-heterocyclic containing delta-opioid receptor modulating compounds, methods of using and making the same
CA3054122A1 (en)	2017-03-02	2018-09-07	Ube Industries, Ltd.	Therapeutic agent for alcohol use disorders
CN108250088B (zh) *	2018-01-04	2020-10-30	四川之江高新材料股份有限公司	N，n，n′-三甲基-n′-羟乙基双氨基乙基醚的制备方法
CN115825305B (zh) *	2022-10-21	2024-09-20	昆明理工大学	一种分子印迹固相微萃取纤维及其制备方法与应用

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3065230A (en) *	1959-03-16	1962-11-20	Burroughs Wellcome Co	Azabicyclohexanes and method of preparing them
IL86061A (en) *	1987-04-16	1992-07-15	Lilly Co Eli	Derivatives of trans-3,4-isomer of 4-methyl-4-phenyl-piperidines,process for their preparation and pharmaceutical compositions containing them
US5159081A (en) *	1991-03-29	1992-10-27	Eli Lilly And Company	Intermediates of peripherally selective n-carbonyl-3,4,4-trisubstituted piperidine opioid antagonists
DE4341403A1 (de) *	1993-12-04	1995-06-08	Basf Ag	N-substituierte 3-Azabicycloalkan-Derivate, ihre Herstellung und Verwendung
PE20001420A1 (es) *	1998-12-23	2000-12-18	Pfizer	Moduladores de ccr5
TWI244481B (en) *	1998-12-23	2005-12-01	Pfizer	3-azabicyclo[3.1.0]hexane derivatives useful in therapy

2000
- 2000-06-23 GB GBGB0015562.2A patent/GB0015562D0/en not_active Ceased
2001
- 2001-06-06 DO DO2001000187A patent/DOP2001000187A/es unknown
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- 2001-06-07 YU YU91802A patent/YU91802A/sh unknown
- 2001-06-07 DZ DZ013368A patent/DZ3368A1/xx active
- 2001-06-07 HR HR20020998A patent/HRP20020998A2/hr not_active Application Discontinuation
- 2001-06-07 KR KR1020027017503A patent/KR20040002386A/ko not_active Ceased
- 2001-06-07 WO PCT/IB2001/001035 patent/WO2001098267A1/en not_active Ceased
- 2001-06-07 CZ CZ20023967A patent/CZ20023967A3/cs unknown
- 2001-06-07 BR BR0111867-6A patent/BR0111867A/pt not_active IP Right Cessation
- 2001-06-07 NZ NZ523141A patent/NZ523141A/en unknown
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- 2001-06-07 AU AU62591/01A patent/AU781837B2/en not_active Ceased
- 2001-06-07 CN CNA018116086A patent/CN1639121A/zh active Pending
- 2001-06-07 EP EP01936728A patent/EP1292574A1/en not_active Withdrawn
- 2001-06-07 SK SK1717-2002A patent/SK17172002A3/sk unknown
- 2001-06-07 CA CA002412188A patent/CA2412188A1/en not_active Abandoned
- 2001-06-07 MX MXPA02012878A patent/MXPA02012878A/es unknown
- 2001-06-07 IL IL15342701A patent/IL153427A0/xx unknown
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- 2001-06-07 PL PL01365956A patent/PL365956A1/xx not_active Application Discontinuation
- 2001-06-07 OA OA1200200386A patent/OA12293A/en unknown
- 2001-06-12 PA PA20018519401A patent/PA8519401A1/es unknown
- 2001-06-21 PE PE2001000604A patent/PE20020253A1/es not_active Application Discontinuation
- 2001-06-21 AR ARP010102957A patent/AR028969A1/es unknown
- 2001-06-21 UY UY26787A patent/UY26787A1/es not_active Application Discontinuation
- 2001-06-22 TN TNTNSN01094A patent/TNSN01094A1/fr unknown
- 2001-07-06 UA UA20021210406A patent/UA73176C2/uk unknown
2002
- 2002-11-28 BG BG107329A patent/BG107329A/xx unknown
- 2002-11-28 IS IS6637A patent/IS6637A/is unknown
- 2002-12-16 MA MA26955A patent/MA26915A1/fr unknown
- 2002-12-19 ZA ZA200210278A patent/ZA200210278B/xx unknown
- 2002-12-20 NO NO20026168A patent/NO20026168L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
NZ523141A (en)	2005-06-24
DZ3368A1 (fr)	2001-12-27
BG107329A (en)	2003-07-31
EP1292574A1 (en)	2003-03-19
MA26915A1 (fr)	2004-12-20
CA2412188A1 (en)	2001-12-27
UY26787A1 (es)	2002-01-31
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CN1639121A (zh)	2005-07-13
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IS6637A (is)	2002-11-28

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